Spinal cord injuries (SCI) and diseases are continuing medical conditions without adequate treatment options.
Within the central nervous system many pathological neurological conditions, including spinal cord injuries, involve altered function of not only neurons but also macrophages and glial cells, including oligodendrocytes and astrocytes. Studies suggest that glial response to the injury participates in formation of the astroglial scar and development of the “hostile” environment at the injury epicenter. Increased levels of inhibitory factors in and around the glial scar in damaged spinal cord are known to contribute to: (i) neuronal death that progresses during the course of secondary injury, restricted regeneration of damaged axons, (iii) disrupted myelination of lesioned and survived axons, and (iv) limited transmission through the surviving axons. These deficits are major burdens that restrict recovery of function following spinal cord injury or disease.
The role of glia in SCI is dual. They may contribute to secondary damage or be neuroprotective. The major glial response to SCI includes: (i) secretion of glia-derived scar-related inhibitory factors, such as chondroitin sulphate proteoglycans (CSPGs), including NG2, a major inhibitory factor restricting axonal regeneration and blocking axonal conduction, (ii) changes in transition of oligodendrocyte precursor cells (OPCs, known to be NG2-positive) into mature oligodendrocytes, thus effecting axonal myelination and remyelination, (iii) functional changes in astrocytes (i.e. reactive astrogliosis), which are major contributors to glial scar and known to secrete both growth promoting and inhibitory factors after SCI, (iv) activation of microglia, the number of which is rapidly elevated in the vicinity of the injury. Another cell type, macrophages, also accumulate close to the injury epicenter, and are known to be derived from both microglia and haematogenous macrophages. In many cases these cells are referred to as macrophages/microglia because it is difficult to discriminate between the activated microglia and macrophages in the injured central nervous system (CNS). Macrophages/microglia are among the major cells participating in the inflammatory cell response following SCI.
What is desired is a suitable method of improving spinal cord functionality after injury or disease. Embodiments of the present disclosure provide methods that address the above and other issues.